Thanatophoric Dysplasia Workup
- Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Luis O Rohena, MD more...
The following studies are indicated in suspected cases of thanatophoric dysplasia (TD):
- Chromosome analysis (karyotype) to determine the presence or absence of chromosomal abnormalities
- DNA molecular testing for FGFR3 using targeted and sequence mutation analyses
A study by Chitty et al suggested that next-generation sequencing (NGS) is more sensitive than polymerase chain reaction assay and restriction enzyme digest (PCR-RED) in screening for monogenic disorders, including thanatophoric dysplasia. In the study, which used cell-free DNA from maternal blood, NGS and PCR-RED were performed in the diagnosis of achondroplasia and thanatophoric dysplasia, with NGS being 96.2% accurate, compared with 88.6% for PCR-RED.
Prenatal ultrasonography[7, 8] and CT scan assessments may be diagnostically helpful as follows:
See the list below:
- Two-dimensional (2D) ultrasonography reveals polyhydramnios, growth deficiency, ventriculomegaly, a narrow thorax, flattened vertebrae and micromelia
- Three-dimensional (3D) ultrasonography may reveal the fetal face, scapular anomalies, and chest hypoplasia better than 2D ultrasonography
- A study by Wang et al indicated that the prenatal identification of temporal lobe dysplasia by ultrasonography may aid in the identification of thanatophoric dysplasia; the study found that out of 24 cases of thanatophoric dysplasia, 16 (67%) demonstrated ultrasonographic evidence of temporal lobe dysplasia
- Prenatal 3D CT scanning may complement ultrasonographic findings in cases in which fetal skeletal dysplasia is suspected, but no specific diagnosis can be made using ultrasonography alone; further studies on clinical performance and risk-benefit analysis are needed before 3D CT scanning is incorporated into standard practice guidelines
Postnatal radiography and other imaging studies (CT, MRI) reveal the following:
- Enlarged skull and a small foramen magnum with potential evidence of brain stem compression
- CNS abnormalities such as hydrocephalus, brainstem hypoplasia, temporal lobe malformations, neuronal migration abnormalities
- Flattened vertebral bodies (platyspondyly) with wide intervertebral spacing
- Rhizomelic shortening and irregular metaphyses of the long bones and "telephone receiver–shaped" bowed femurs
See the list below:
- Histologic evaluation of long bone structure in thanatophoric dysplasia shows disruption of endochondral ossification but not of periosteal ossification.
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